Single Photon Emission Computed Tomography (SPECT) as a form of nuclear medicine imaging is used to show how organs, systems and different molecular processes in the human body are functioning. Acquisition of 3d SPECT images takes about 20-40 minutes, depending on procedure, and during this time it is usually assumed that the ‘function’ that is being imaged is stationary, not changing in time during the duration of the scan. During the SPECT scan the 1 to 3 imaging detector heads are rotating slowly around the patient recording views of the patient's body or organs from different angles. This is how the tomographic information is collected to reconstruct later the patient images in 2d views-slices through the 3d reconstructions. However, most of the body functions are dynamic and this leads to the loss of this important dynamic information and even to errors (artifacts) showing up in the reconstructed images. In some studies this dynamic 3d information is crucial to the study and it often prevents the use of SPECT in some important biological research and forces the researchers to move to Positron Emission Tomography (PET), where the imaging is acquired by a ring of many small stationary detectors. The basic principle of PET imaging combined with the relatively large, compared to SPECT, number of imaging modules provides sufficient number of viewing tomographic angles to produce high quality 3d reconstructions. However, PET technique requires development of special positron imaging agents while most of the existing agents are of a single photon type, applicable to SPECT. Therefore, there is a strong motivation to remedy this traditional limitation of the standard SPECT with few and slowly rotating detector heads. First, new reconstruction techniques have been developed which allow the generation of dynamic images from a normal clinical data acquisition. However, these techniques require complicated system modeling and assumptions about the dynamic processes that are to be unfolded in 3d reconstructions from the limited dynamic angular data obtained in a normal clinical acquisition with a slowly rotating gamma cameras.
In an effort to avoid these approximations, stationary brain SPECT systems were designed with a relatively large (12-24) number of detector heads compared to the standard SPECT, but still small compared to the optimal number of angular projections required in an artifact-free high resolution SPECT. To increase the number of available simultaneous projections, some of these stationary SPECT designs use multiple pinhole collimators. In some designs, the collimators are rotating to increase the number of projections. However, these special clinical SPECT systems are at present only limited to imaging the brain.
High resolution SPECT molecular imaging of small animals such as mice and rats used in models of many human diseases, typically requires that even more planar images are acquired by stepping a few (sometimes as little as one to three) imaging detector heads around the animal. Such scans may consist of over a 100 individual images or projections obtained by stepping a rotating gantry by the same angular increment of an order of a few degrees and acquiring an image typically for 5-20 seconds. This is called a step-and-shoot mode of scanning. In other scans imaging heads are permitted to continuously and slowly rotate about the object and the individual images-projections are obtained by combining collected data from a range of viewing angles falling within an angle increment. Independently of the version of this type of a scan with a slow rotation speed of the imaging heads, a high a number of different angular views of the object-animal with distributed gamma activity is necessary to obtain high quality, artifact-free 3d reconstructions of the activity distributions (uptakes) in the animal organs, in tumors, etc. Typically the full rotation scanning procedure over 360 degrees takes from 20-60 minutes, or even longer. After the scan (involving at most one rotation only) is complete, the individual images-projections obtained for each stepping angle are read into a proper 3d reconstruction algorithm and results are presented in the form of 2d slices—planar cuts through the object-animal.
The most relevant prior art is the stationary ring SPECT system designed for small animals at the University of Arizona (1) Barrett et al. High-Resolution Imaging with 99 mTc-Glucarate for Assessing Myocardial Injury in Rat Heart Models Exposed to Different Durations of Ischemia with Reperfusion, Z. Liu, H. H. Barrett, G. D. Stevenson, G. A. Kastis, M. Bettan, L. R. Furenlid, D. W. Wilson, and K. Y. Pak, J. Nucl. Med., Jul. 1, 2004; 45(7): 1251-1259; 2) Imaging recognition of multidrug resistance in human breast tumors using 99m Tc-labeled monocationic agents and a high-resolution stationary SPECT system Zhonglin Liu*, Gail D. Stevenson, Harrison H. Barrett, George A. Kastis, Michael Bettan, Lars R. Furenlid, Donald W. Wilson, James M. Woolfenden, Nuclear Medicine and Biology 31 (2004) 53-65 www.elsevier.com/locate/nucmedbio; and 3) FastSPECT H: A Second-Generation High-Resolution Dynamic SPECT Imager, Lars R. Furenlid, Donald W. Wilson, Yi-chun Chen, Hyunki Kim, Philip J. Pietraski, Michael J. Crawford, and Harrison H. Barrett, IEEE TRANSACTIONS ON NUCLEAR SCIENCE, VOL. 51, NO. 3, June 2004, 631) based on a modified stationary brain SPECT (A stationary hemispherical SPECT imager for three-dimensional brain imaging, R K Rowe, J N Aarsvold, H H Barrett, J C Chen, W P Klein, B A Moore, I W Pang, D D Patton and T A White, Journal of Nuclear Medicine, Vol 34, 1993, Issue 3, 474-480). The motivation for that system was similar to the system described herein, but with even more strict requirements for fast temporary performance of under 1 second to enable dynamic cardiac imaging. However, because that stationary system is composed of a fixed number (16) of imaging modules, only the angular sampling accuracy of much less than the desired more than 100 samplings per 360 deg (3 deg or less per angular increment) is possible. This leads to problems with image reconstruction, such as artifacts, as mentioned above.
Another important difference between that rather large stationary system and the compact dynamic system described here is that to obtain high spatial resolution performance, the Arizona imager is equipped with pinhole collimators attached to larger imaging heads with moderate intrinsic spatial resolution. The detector heads are operating at a magnification factor of ˜3 to compensate for their moderate intrinsic spatial resolution. In this way, the useful field-of-view is highly reduced and limited (by design) to primarily accurately image animal organs, such as the brain, heart, etc, and only a whole small mouse can be imaged. Therefore, that system cannot provide a dynamic image of a larger whole rodent animal such as a rat. In addition to the fixed size issue, the stationary SPECT design of Barrett et al uses few pinholes (one per module) and therefore cannot be optimized for high efficiency. Using pinhole collimators was not only necessary to achieve high spatial resolution, but it was also the only practical way to place 16 detector heads on a (large diameter) ring to provide the 16 independent views-projections. In our parallel-hole close geometry configuration it would not be possible to place even that small a number of modules on a ring and close to an animal. As explained before, the close detector distance to the object-animal is absolutely necessary to obtain the best possible combination of system spatial resolution and sensitivity, when using parallel-hole collimators.
As the quality of SPECT reconstruction depends on the number of independent views-projections and also in a crucial way on event statistics through detection efficiency (or on signal to noise ratio), the obtained images by the Arizona scanner indeed show the effects of limits in these two parameters.
Very high resolution stationary animal SPECT to image small objects such as a brain of a mouse, was proposed recently by Beekman et al (Design and simulation of a high-resolution stationary SPECT system for small animals, Freek J Beekman 1, 2 and Brendan Vastenhouw 1, 2, Phys. Med. Biol. 49 (2004) 4579-4592 PH: S0031-9155(04)80035-6) by combining very high resolution pinhole imaging with large number of pinholes and with compact high-resolution gamma cameras. The system described herein solves the problem of the limited sensitivity-resolution trade-off that hampers contemporary small animal SPECT. One of the proposed designs, U-SPECT-III, uses a set of 15 detectors placed in a polygonal configuration and a cylindrical collimator that contains 135 pinholes arranged in nine rings. Each ring contains 15 gold pinhole apertures that focus on the center of the cylinder. A non-overlapping projection is acquired via each pinhole.
High-resolution scintillation detectors can be built based on angled columnar CsI(Tl) scintillator in such a way that it would eliminate the depth-of-interaction problem encountered with pinhole cameras. The expected intrinsic detector resolution is better than 150 μm. While this stationary SPECT design is theoretically optimized for very high sub-mm spatial resolution and high efficiency by using multi-pinhole collimator system, by design it covers only a small field of view (FOV) such as a brain of a mouse or a rat. This complicated concept cannot be easily adapted to a larger FOV such as a whole rat, or even a mouse.
In addition to the above dedicated animal SPECT efforts, the basis for several other attempts to build a dynamic small animal SPECT was the prior art related to the dynamic brain SPECT.
A stationary annular NaI(Tl) crystal and a rotating collimator system was for example used many years ago in a dedicated brain-imaging instrument (Radionuclide Annular Single Crystal Scintillator Camera with Rotating Collimator, S. Genna and S.-C. Pang, U.S. Pat. No. 4,584,478, Apr. 22, 1986; Genna S and Smith A P. The development of ASPECT, an annular single crystal brain camera for high efficiency SPECT. IEEE Trans Nucl Sci. 1988; NS-35: p. 654-658; and Holman B L, Carvalho P A, et al. Brain perfusion SPECT using an annular single crystal camera: initial clinical experience. J Nucl Med. 1990; 31: p. 1456-1461). More recently, a human “super rapid dynamic SPECT” (CERASPECT a brain-dedicated SPECT system. Performance evaluation and comparison with the rotating gamma camera, F Zito et al 1993 Phys. Med. Biol. 38 1433-1442) was further developed to make it even faster and used to evaluate retention process of 99 mTc-ECD in ischemic lesions (Development of super rapid dynamic SPECT, and analysis of 99 mTc-ECD dynamics as determined in ischemic lesion, Komatani A, Sugai Y, Hosoya T, Eur J Nucl Med 2001; 28 (Suppl): S1223, and Development of “super rapid dynamic SPECT,” and analysis of retention process of 99 mTc-ECD in ischemic lesions: Comparative study with 133Xe SPECT, Akio KOMATANI, Yukio SUGAI and Takaaki HOSOYA, Annals of Nuclear Medicine Vol. 18, No. 6, 489-494, 2004). This stationary system is built as a ring of 21 scintillation modules, each made with three PMTs, attached to a continuous cylindrical scintillator gamma sensor. The patient's head is inserted in the cylindrical opening of the imager. The system is equipped with special high efficiency parallel hole collimators, one per each scintillation detection head. Time bins for dynamic tomographic projections as short as 2 sec are possible with this system. While offering good dynamic performance for the above clinical applications on human subjects, the system does not exhibit high enough spatial resolution to be used on small animals.
Focusing type collimators are used in another new dedicated Neurofocus Scanned Focal Point scanner (SFP™) brain imager (EVALUATION OF THE HIGH RESOLUTION NEUROFOCUS SPECT DEVICE FOR SMALL ANIMAL IMAGING, J. P. Seibyl, H. A. Stoddart, D. Martin, E. Smith, G. Wisniewski and H. F. Stoddart, Institute for Neurodegenerative Disorders, New Haven, Conn. and NeuroPhysics Corp, Shirley, Mass.). produced by Neurophysics Corporation. Twelve modules of this stationary ring SPECT cover axial FOV of 20 cm and are equipped with diverging collimators. As a result, spatial resolution on the central axis is only 3 mm FWHM, which is only marginally applicable to small animal imaging.
Nevertheless, several groups modified the human brain SPECT systems to adapt them for small animal imaging, sometimes with the dynamic imaging in mind.
An NIH group Green et al, (A NOVEL MOUSE SPECT SCANNER USING AN ANNULAR SCINTILLATION CAMERA, D. W. Jones*, A. L. Goertzen†, S. Riboldi†, J. Seidel†, K. Li‡, M. V. Green†, Abstracts of the AMI Annual Meeting 2003 109; and First Results from the High-Resolution mouse SPECT Annular Scintillation Camera. L. Goertzen 1, 2, D. W. Jones 3, J. Seidell, K. Lil, M. V. Green†, presented at the 2004 IEEE Medical Imaging Conference, Rome, 2004) modified a CERASPECT annular camera brain imager for small animal imaging by adding rotating pinhole collimators. This modified imager offering the possibility of dynamical SPECT imaging and dual tracer SPECT studies, is called mouseSPECT and uses collimator array comprised of eight equally spaced tungsten pinholes that continuously rotate around the prone and stationary animal at up to 1 rev/10 s. The pinholes simultaneously project eight non-overlapping images onto the annular scintillation crystal of a scanner. While the primary intention of that design was an 8-fold increase in sensitivity compared to a single rotating gamma camera with the same type single pinhole collimation, the relevant feature of that scanner is its ability to quickly capture a full 360 deg projection set of the object (animal) necessary to achieve 3d dynamic reconstructions.
The individual projection images from the pinholes are formed on the 31 cm diameter by 13 cm wide solid NaI(Tl) scintillator annulus. The intrinsic resolution of the imager (@140 keV) is 3.5 mm FWHM. The magnification geometry of the object-collimator-detector is so adjusted as to define the transaxial field of view of about 25 mm to allow imaging of a mouse. The 28 mm pinhole radius of rotation and the annular radius of the scanner combine to give a magnification of approximately 4.5. 0.5 mm and 1.0 mm diameter interchangeable pinhole inserts were used to allow a tradeoff between resolution and sensitivity depending on study requirements. Data is currently acquired in step-and-shoot mode, however the system is capable of list mode acquisition with the collimator continuously rotating. Images are reconstructed using a cone-beam OSEM method. The reconstructed spatial resolution of the system is 1.7 mm and the sensitivity at the centre of the FOV is 13.8 cps/microCi.
The above mentioned NeuroFocus brain imager was also tested for small animal imaging. The NeuroFocus is a high efficiency brain-dedicated stationary single photon imaging device utilizing 12 scanning detector heads fitted with 1 inch NaI crystals and 800 hole focused collimators with the potential for use in small animal imaging based on ultrahigh resolution while maintaining high count rate response. Measurements of the FWHM of the line spread function were determined for 99 mTc to be about 3 mm FWHM in the center of the field of view, which is marginal for imaging mice, but sufficient for many rat studies.
Non-orbiting tomographic system was proposed by Mosaic Imaging Technology (Non-orbiting tomographic imaging system, DeVito; Raymond P. (Palatine, Ill.); Haines; Edward J. (Marengo, Ill.); Domnanovich; James R. (Elk Grove Village, Ill.) Assignee: Mosaic Imaging Technology, Inc. (Schaumburg, Ill.), U.S. Pat. No. 6,242,743, Jun. 5, 2001). The system described in this patent comprises a plurality of detector modules positioned close to the object and equipped with high-resolution collimators in a combination of application-specific acquisition geometries and non-orbital detector module motion sequences composed of tilting, swiveling and translating motions, and combinations of such motions. Various kinds of module geometry and module or collimator motion sequences were considered. The considered applications include imaging human organs, such as head, breast, extremities (leg), etc, in addition to small animal imaging. However, the main focus of that technical approach is on a stationary aspect of the system that can be used as a bed-side compact imager in clinical applications. The tilting, swiveling and translating motions, are to collect more tomographic projections to assure higher quality imaging and it has merit in the clinical situations with sick bed-ridden patients etc, but this is a rather complicated and not well optimized approach for small animal imaging application.
Finally, among the potentially relevant prior art to mention are the software-based efforts of improving 3d reconstruction of the dynamic SPECT data based on a limited angular information obtained with standard slowly rotating/orbiting clinical SPECT systems. Standard reconstruction techniques do not allow temporal information to be obtained from this inconsistent projection data and may also create serious image artifacts which may lead to errors in diagnosis. Much better results are obtained using tomographic techniques such as PET or (as discussed above) ring camera SPECT where all projections of each image are acquired simultaneously. However, both PET and ring SPECT systems are more expensive and less common than SPECT systems which are available in almost any larger hospital.
The stated ultimate goal of the dynamic SPECT project (dSPECT) is to develop an imaging method suitable for functional dynamic studies which would use standard clinical equipment and standard data acquisition protocols and provide temporal in addition to 3-dimensional spatial information about the changes of activity distribution in the body. The dynamic SPECT (dSPECT) method can be used with all standard, currently available SPECT systems which means single, double and triple head cameras. The result of the dSPECT reconstruction, which includes attenuation and resolution recovery corrections, is a 4D data set, composed of a time-series of 3D SPECT images (3D movies). The dSPECT reconstruction is based on a mathematical optimization procedure where all the dynamic projections are considered simultaneously. It has been shown that dSPECT reconstructed dynamic images have better signal to noise ratios than those obtained by the “fast-rotation” method, where several data sets are reconstructed separately.
While showing some interesting possibilities, the above effort will most probably never be able replace the full data set obtained by the relatively rapidly rotating system described herein, and therefore is not considered an option for small animal imaging.
In a very recent paper Maddula et al (Dynamic Cardiac SPECT Imaging Using a Stationary SPECT Camera, R. Maddula, R. Clackdoyle, J. Roberts, E. Di Bella, Z. Fu, presented at the IEEE 2004 Medical Imaging Conference, Oct. 16-22 2004, Rome, Italy), describe a novel clinical cardiac SPECT camera (DyRoSH system) with the capability to collect full tomographic data every 2 seconds. The proposed camera uses three stationary detectors mounted with slant-hole collimators that rotate at about 30 rpm. Because the detectors are stationary, they can be placed much closer to the patient for improved spatial resolution. With Monte Carlo simulations and list-mode reconstructions, the authors compared the performance of conventional 3-headed SPECT with the proposed stationary SPECT system to estimate the kinetic parameters of two-compartmental model of myocardial perfusion. The study separated the effects of fast temporal scanning speed and better spatial resolution of DyRoSH scanner in estimating the kinetic parameters of myocardial perfusion accurately. The proposed system showed better accuracy in estimating kinetic parameters compared to conventional SPECT scanner. Again, the concept of rotating slant collimators limits the useful field of view and while it is well adapted to imaging of a human heart it cannot be easily scaled down and translated to high spatial resolution imaging of a whole small animal, such a rat, requiring about 20 cm FOV along the length of the animal.
In summary, the previously proposed fast dynamic SPECT designs for small animals were based on a fixed diameter concept, where the system opening was pre-defined and as large as to accommodate the largest animal to study. For example, the scintillator in the form of annulus offers full-angle coverage, high system efficiency and high imaging granularity but due to the above mentioned size compromises, the resulting spatial resolution is suboptimal for imaging an object such as a small mouse. The very interesting design with rotating (pinhole or other) collimators allows one to avoid mechanical complexity of our proposed system where the whole set of detector heads with collimators has to rotate and relatively fast around the animal, but again that system does not offer a flexibility to be optimized for a particular imaging geometry. Finally, the pinhole collimator based systems, both rotating and stationary, suffer from small active field of view, and/or poor sensitivity. None of the discussed in the literature designs proposed high sensitivity and high spatial resolution fast dynamic tomographic (SPECT) imaging of a whole animal such as a rat.
Accordingly, there remains a need for a fast dynamic SPECT designs that exhibit high sensitivity and high spatial resolution fast dynamic tomography for small animals. While the gantry apparatus described herein goes far in providing an SPECT apparatus that meets these needs there remains the problem of calibrating the multi-headed tomographic imager in a common spatial coordinate system to provide the high sensitivity and high spatial resolution fast dynamic tomography images desired as described above.